IGF1/IGF1R and microRNA let-7e down-regulate each other and modulate proliferation and migration of colorectal cancer cells. Issue 10 (19th May 2018)

• Record Type: Journal Article
• Authors: Li, Zhenjun; Pan, Weihuo; Shen, Yi; Chen, Zhiliang; Zhang, Lihua; Zhang, Yuping; Luo, Quan; Ying, Xiaojiang
• Is Part Of: Cell cycle. Volume 17:Issue 10(2018)
• Page Start: 1212
• Page End: 1219
• Publication Date: 2018-05-19
• Subjects: Insulin-like growth factor 1 (IGF1) -- insulin-like growth factor 1 receptor (IGF1R) -- microRNA let-7e -- colorectal cancer; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2018.1469873
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: MicroRNA let-7 has been reported to be down-regulated in several human cancers and is now characterized as a tumor suppressor. IGF1R is over-expressed in many cancers and IGF1/IGF1R pathway is attractive target for anticancer therapy. However, the crosstalk between let-7 and IGF1/IGF1R are largely unknown. The present study showed IGF1R were significantly over-expressed in colorectal cancer tissues compared with adjacent normal tissues through immunohistochemical analysis. qRT-PCR results showed that let-7a, let-7b and let-7e were down-regulated in colorectal cancer tissues. Bioinformatics analysis revealed that both IGF1 and IGF1R mRNA are potential targets for let-7 miRNA family. Ectopic transfection of let-7e led to a significant reduction in IGF1R at protein level and their downstream Akt inhibition, as well as a reduction in cell proliferation, migration and invasion in colorectal cancer cells, while inhibition of let-7e enhanced the expression of IGF1R. On the other hand, IGF1 stimulation can significantly down-regulate the expression of let-7e in colorectal cancer cells. Taken together, our findings identify a negative feedback regulation between let-7e and IGF1/IGF1R, and suggest that let-7e could be used in IGF1R-targeted therapeutics in anticancer therapy. Abbreviations: IGF1 : insulin-like growth factor 1; IGF1R : IGF1 receptor; miRNA : microRNA; CRC : colorectal cancer; EGFR : epidermal growth factor receptor; HRP : horseradish peroxidase; MTT : 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide; p-Akt: phospho-Akt; PI3K : phosphoinositide 3-kinase; qRT–PCR: quantitative reverse transcription–PCR; IHC : immunohistochemical; siRNA : small interfering RNA; 3′-UTR: 3′-untranslated region